This project has clinical and basic components. We continue in our endeavors to understand the determinants of prognosis in the pediatric non-Hodgkin's lymphomas and to develop improved combination chemotherapy. At the present time our clinical therapeutic studies are directed towards a) attempting to ameliorate toxicity encountered in a successful combination regimen for patients with small non-cleaved cell (SNCL) and large cell lymphomas; and b) documenting the late effects encountered by patients treated on our lymphoma protocols. Our basic studies are directed towards the elucidation of the molecular biology and molecular epidemiology of the SNCL. Major areas of investigation include a) detailed characterization of the non-random chromosomal translocations (particularly 8; 14 translocations) associated with the SNCL, with a view to understanding the immediate causes of neoplastic behavior in these tumors and the determinants of geographic and clinical heterogeneity; b) the elucidation of the nature of the association of Epstein-Barr virus (EBV) with the SNCL; c) the examination of selected biological and clinical aspects of lymphomas associated with HIV infection; d) the elucidation of the significance of the mutations in the coding region of the c-myc gene recently discovered in this laboratory; and 3) the exploration of other molecular abnormalities of potential interest in the SNCL, in particular mutations in p53. Stemming from these studies, we are also investigating the possibility that the molecular abnormalities can be used as a target for tumor-specific treatment approaches.